Terpene-Functionalized 3,5-Bis(benzylidene)-4-piperidones: Synthesis, Cytotoxicity Properties, In Silico and In Vitro Studies

Aleksandrova Y. Neganova M. Tapalova A. Sokolova A. Rodionov A. Shagina I. Appazov N. Brel V.
October 2025 Multidisciplinary Digital Publishing Institute (MDPI)

Chemistry (Switzerland)
2025 #7 Issue 5

To develop new hybrid anticancer agents, 3,5-bis(benzylidene)-4-piperidone scaffolds (compounds 1–6) were functionalized with (1R)-borneoyl chloroacetate (8) or (1S)-camphorsulfonyl chloride (10). Covalent attachment of the camphorsulfonyl moiety via N-sulfonylation yielded hybrid molecules (16–21) that exhibited selective cytotoxic and cytostatic activity against cancer cells, with submicromolar IC₅₀ values. In silico ADME analysis indicated that these camphorsulfonyl-conjugated piperidones have improved drug-like properties (enhanced absorption, metabolism, and bioavailability) compared to curcumin. The most potent analogs were halogen-substituted and trimethoxy-substituted analogs, which showed the strongest tumor cell growth inhibition while sparing normal cells. Overall, this terpene-functionalization strategy addresses curcumin’s pharmacokinetic limitations and improves its anticancer profile. These hybrid molecules hold promise as potential anticancer agents.

(1R)-(-)-borneoyl chloroacetate , (1S)-(+)-camphorsulfonyl chloride , 3,5-bis(benzylidene)-4-piperidones , ADME profile , antiproliferative potential , cytotoxicity , reaction of N-sulfonylation , terpenes

Text of the article Перейти на текст статьи

Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, 119991, Russian Federation
Laboratory of Engineering Profile “Physical and Chemical Methods of Analysis”, Korkyt Ata Kyzylorda University, Kyzylorda, 120014, Kazakhstan
Department of Biology, Geography and Chemistry, Korkyt Ata Kyzylorda University, Kyzylorda, 120014, Kazakhstan
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russian Federation

Nesmeyanov Institute of Organoelement Compounds
Laboratory of Engineering Profile “Physical and Chemical Methods of Analysis”
Department of Biology
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry

10 лет помогаем публиковать статьи Международный издатель

Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026